After GABA and glycine are released from the presynaptic terminal, they are taken back up into the nerve terminal and neighboring glia by high-affinity Na+-Cl−–coupled membrane transporters. These Na+-Cl− transporters are part of what is called the solute carrier 6 (SLC6) family of transporters that also includes those for the biogenic amine neurotransmitters, but it is distinct from those for glutamate. Transport of the neurotransmitter into the cell is accomplished by symport with two Na+ and one Cl− ion. Four GABA transporter (GAT1, GAT2, GAT3, and BGT1) genes have been identified; however, GAT1 and GAT3 are the ones that are highly expressed in the CNS. Depending on region and species, they may be expressed in neurons and/or in glia. There are two main glycine transporters, GlyT1 and GlyT2. GlyT1 is found predominantly on astrocytes and is present throughout the CNS. In contrast, GlyT2 is located on glycinergic nerve terminals and is largely restricted to the spinal cord, brainstem, and cerebellum.
Many of the neurotransmitters in this category may be familiar because they have roles outside the nervous system, often as hormones. Among the amines known to act as neurotransmitters are dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), serotonin (5-hydroxytryptamine [5-HT]), and histamine. Dopamine, norepinephrine, and epinephrine are catecholamines, and they share a common biosynthetic pathway that starts with the amino acid tyrosine. Tyrosine is converted to L-dopa by the enzyme tyrosine hydroxylase. L-Dopa is then converted to dopamine by dopa-decarboxylase. In dopaminergic neurons, the pathway stops here. In noradrenergic neurons, another enzyme, dopamine β-hydroxylase, converts dopamine to norepinephrine. Epinephrine is obtained by adding a methyl group to norepinephrine via phenylethanolamineN-methyl transferase. In serotoninergic neurons, serotonin is synthesized from the essential amino acid tryptophan. Tryptophan is first converted to 5-hydroxytryptophan by tryptophan 5-hydroxylase, which is then converted to serotonin by aromatic L-amino acid decarboxylase. Finally, in histaminergic neurons the conversion of histidine to histamine is catalyzed by histidine decarboxylase.
Removal of synaptically released biogenic amines is generally accomplished by reuptake into glia and neurons via transporters belonging to the Na+-Cl−–dependent transporter family. The catecholamines are then degraded by two enzymes, monoamine oxidase and catechol Omethyltransferase.
Atleastfivetransporters(EAAT1toEAAT5,inwhichEAAT standsforexcitatory amino acid transporter)thatcarryglutamateacrosstheplasmamembranehavebeenidentified.TheyareallpartoftheNa+-K+–dependentfamilyoftransporters.InwardmovementofeachglutamatemoleculeisdrivenbythecotransportofthreeNa+ ionsandoneH+ ionandthecountertransportofoneK+ ionoutofthecell(see